This protocol addresses patients with unresectable stage III or metastatic (stage IV) melanoma in whom a BRAF V600 mutation has been confirmed. The mutation status is a key determinant of systemic treatment selection at first line.
Confirmation of a BRAF V600 mutation opens additional first-line treatment pathways beyond those available for BRAF wild-type disease. Both immunotherapy-based combinations and BRAF-targeted regimens may be appropriate, with choice guided by clinical factors including disease pace and patient eligibility.
When access to anti-PD-1-based immunotherapy is limited or a patient is ineligible for it, BRAF inhibitor plus MEK inhibitor combinations represent an evidence-supported alternative in this population.
For eligible patients, a preferred immunotherapy combination is the first-line standard when a rapid response is not required; for BRAF-mutated disease, BRAF inhibitor plus MEK inhibitor combinations are an established alternative when immunotherapy is not suitable.
For patients with unresectable disease, first-line ipilimumab–nivolumab is a preferred option for all patients regardless of BRAF status when this can be safely delivered for the first few months (i.e. when a rapid response is not required due to aggressive/symptomatic disease) [I, A].
If anti-PD-1-based therapy is not available or patients are considered ineligible for its use, BRAFi–MEKi combination therapy (dabrafenib–trametinib [ESMO-MCBS v1.1 score: 5]; vemurafenib–cobimetinib [ESMO-MCBS v1.1 score: A/5]; binimetinib–encorafenib [ESMO-MCBS v1.1 score: A/5]) is also an option in the first line for patients with BRAF-mutated melanoma [I; A; ESCAT score: I-A].
In case of BRAF-mutated melanoma, additional first-line options are provided by BRAFis and MEKis.
View source ↗